Vaccine research gets a shot in the arm

IT'S a fact too easily overlooked: vaccines are huge life-savers. They prevent up to 3 million deaths a year, according to the World Health Organization. That's pretty impressive, and there is much more to come. Advances in biotechnology are giving vaccine research a shot in the arm, increasing the opportunities to develop new vaccines – and careers.

As Edward Jenner discovered more than 200 years ago, exposing people to a harmless pathogen can offer them protection against a dangerous, related one. Back then, Jenner injected people with cowpox to protect them against the much more harmful smallpox. In the intervening centuries, we became adept at making vaccines from dangerous microbes that we had first made harmless.

"It was a very simple approach. You attenuated or killed the pathogen, and that was your vaccine," says Margaret Ackerman at Thayer School of Engineering at Dartmouth College in Hanover, New Hampshire. "When that worked as a vaccine it was great, but when it didn't, it was hard to know where to go next."

Today, we do have somewhere else to go. Biotechnology is opening up new avenues for vaccine development – what Julie Louise Gerberding calls, "the new vaccine frontier". "We're really in an environment where we can look forward to a complete modernisation of the whole vaccinology process," says Gerberding, who leads the vaccine division at pharmaceutical company Merck.

One approach that has emerged over recent decades is to create proteins in the lab that mimic those found in pathogens. These proteins – or antigens – are often found on the surface of microorganisms and can be used to prime a person's immune system to destroy the invaders.

Ackerman, who trained as a protein engineer, is trying to make proteins that trigger fierce immune reactions by taking the antigens already expressed by pathogens and tweaking them. "Using protein engineering tools, we can look at a million or a billion variants of an antigen and pull out variants that we think would make a better vaccine," says Ackerman.

Knowing the genes of pathogens and the proteins they express has really helped in these endeavours. "We finally have the toolkit – computationally and genomically – to do this much more effectively and rationally," says Ackerman. The people who will be best placed to make use of that toolkit are those with training in bioinformatics and computing, as well as genetics, she says. "Those are all skills that are in demand."

Ackerman's team is one of many working on a vaccine for HIV, a virus that kills several million people every year and for which, as yet, no effective vaccine exists (see "World's most wanted vaccines"). Malaria, another big killer, is one of the targets under investigation at GlaxoSmithKline (GSK). The pharmaceutical company is part of an international collaboration that has developed a potential vaccine for the disease.

GSK Vaccines is recruiting team members at its research and development centre in Brussels, Belgium. "At the moment there is hiring going on at all levels – from people who are just leaving university, up to the new leaders and vice-presidents in the organisation," says Ingrid Kraaijbeek, talent acquisition leader at GSK Vaccines. The company tends to see a lot of applications from people who have worked as pharmacists and doctors. "People say: 'I've been on the treating side and I want to move into the preventing side'," says Kraaijbeek.

Other groups are attempting to create vaccines solely from strands of DNA that code for a target pathogen's antigens. Human cells take up these strands and produce the foreign antigens themselves. The antigens provoke a protective immune response against the pathogen. "We are seeing a lot of progress in this area," says Shan Lu, an immunologist at the University of Massachusetts Medical School and president of the International Society for Vaccines.

Gregory Poland, founder of the Mayo Clinic's Vaccine Research Group in Rochester, Minnesota, hopes the use of genomic technologies will lead to the development of personalised vaccines. "We can figure out what genetic variations an individual has that might pose an obstacle to protective immunity, and then reverse-engineer a vaccine candidate around that obstacle," he says. Poland reckons doctors will be able to use the technology to predict whether a person is likely to respond to a vaccine, or if they are at risk of side effects.

Many vaccinologists these days, including Poland, are also developing vaccines for pathogens that do not pose an immediate threat. "I work with the US Department of Defense to help devise countermeasures to bioterror," says Poland, who is working to improve vaccines for smallpox and anthrax.

Biodefence research has received huge funding in recent years. Last year alone, the US Department of Health and Human Services allocated $400 million to three centres for producing vaccines against potential bioweapons. "There's a large amount of money in the US, the UK and other European countries" for such research, says Poland. "We only have two licensed vaccines against bioterrorism agents – anthrax and smallpox – and that's it. There's a lot of work to do." In the UK, much of this work is done by the UK government's Defence Science and Technology Laboratory (DSTL) at Porton Down in Wiltshire.

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